Perspective of ions and messengers: an intricate link between potassium, glutamate, and cyclic di-AMP.

Potassium and glutamate are the most abundant ions in every living cell. Whereas potassium plays a major role to keep the cellular turgor and to buffer the negative charges of the nucleic acids, the major function of glutamate is to serve as the universal amino group donor. In addition, both ions are involved in osmoprotection in bacterial cells. Here, we discuss how bacterial cells maintain the homeostasis of both ions and how adaptive evolution allows them to live even at extreme potassium limitation. Interestingly, positively charged amino acids are able to partially replace potassium, likely by buffering the negative charge of DNA. A major factor involved in the control of potassium homeostasis in Gram-positive bacteria is the essential second messenger cyclic di-AMP. This nucleotide is synthesized in response to the potassium concentration and in turn controls the expression and activity of potassium transporters. We discuss the link between the two major ions, DNA and the second messenger c-di-AMP.